Cytokines as potential biomarkers of liver toxicity

Lacour, Sandrine; Gautier, Jean‐Charles; Pallardy, Marc; Roberts, Ruth

doi:10.3233/cbm-2005-1105

Cited by 81 publications

(55 citation statements)

References 101 publications

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“…Molecular mediators of the immune response, such as TNF-␣, IL-1␤, and IL-6, are related to acute and chronic liver damage (73). The networks of these pro-inflammatory cytokines have been implicated in mediation of hepatic response to xenobiotics as diverse as peroxisome proliferator-activated receptor ligands, acetaminophen, and phenobarbital.…”

Section: Expression Of Proteins and Genes Associated With Drug Metabomentioning

confidence: 99%

In-depth Identification of Pathways Related to Cisplatin-induced Hepatotoxicity through an Integrative Method Based on an Informatics-assisted Label-free Protein Quantitation and Microarray Gene Expression Approach

Cho

Singh

Lee

et al. 2012

Molecular & Cellular Proteomics

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Cisplatin is used widely for treatment of a variety of cancer diseases. Recently, however, the use of cisplatin is restricted because of its adverse effects such as hepatotoxicity. There is no study with current proteomics technology to evaluate cisplatin-induced hepatotoxicity, even if some studies have reported on the hepatotoxicity. In this study, proteomic as well as genomic analyses have been used for identification of proteins and genes that respond to cisplatin treatment in rat primary hepatocytes. To investigate the hepatotoxic effects of cisplatin, rat primary hepatocytes were treated with an IC 20 concentration for 24 h. From proteomic analysis based on label-free quantitation strategy, cisplatin induced 76 up-regulated and 19 down-regulated proteins among 325 distinct proteins. In the mRNA level, genomic analysis revealed 72 up-regulated and 385 down-regulated genes in the cisplatin-treated group. Based on these two analyses, 19 pathways were commonly altered, whereas seven pathways were identified only by proteomic analysis, and 19 pathways were identified only by genomic analysis. Overall, this study explained the mechanism of cisplatin-induced hepatotoxicity with two points of view: well known pathways including drug metabolism, fatty acid metabolism, and glycolysis/TCA cycle and little known pathways including urea cycle and inflammation metabolism, for hepatotoxicity of other toxic agents. Up-regulated proteins detected by proteomic analysis in the cisplatin-treated group: FBP1 (fructose 1,6-bisphosphatase 1), FASN (fatty acid synthase), CAT (catalase), PRDX1 (peroxiredoxin-1), HSPD1 (60-kDa heat shock protein), MDH2 (malate dehydrogenase 2), and ARG1 (arginase 1), and also downregulated proteins in the cisplatin-treated group: TPM1 (tropomyosin 1), TPM3 (tropomyosin 3), and CTSB (cathepsin B), were confirmed by Western blot analysis. In addition, up-regulated mRNAs detected by microarray analysis in the cisplatin-treated group: GSTA2, GSTT2, YC2, TXNRD1, CYP2E1, CYP2C13, CYP2D1, ALDH17, ARG1, ARG2, and IL-6, and also down-regulated mRNAs: CYP2C12, CYP26B1, TPM1, and TPM3, were confirmed by RT-PCR analysis. In case of PRDX1, FASN, and ARG1, they were further confirmed by immunofluorescence analysis. Through the integrated proteomic and genomic approaches, the present study provides the first pathway map related to cisplatin-induced hepatotoxicity, which may provide new insight into the mechanism of hepatotoxicity. Molecular & Cellular

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Section: Expression Of Proteins and Genes Associated With Drug Metabomentioning

confidence: 99%

In-depth Identification of Pathways Related to Cisplatin-induced Hepatotoxicity through an Integrative Method Based on an Informatics-assisted Label-free Protein Quantitation and Microarray Gene Expression Approach

Cho

Singh

Lee

et al. 2012

Molecular & Cellular Proteomics

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“…Abnormally high baseline values of these inflammatory cytokines may be a result of minor infection or underlying undiagnosed pathological conditions. [41][42][43] Also excluded are a few studies reporting values of leptin or adiponectin that are at least 10-fold different, higher or lower, from the mean of other publications. Of the remaining studies, because of the known continuous body composition changes from birth to adulthood (18 years old), 44 only studies on subjects older than 18 years of age were included in the analysis.…”

Section: Data Collectionmentioning

confidence: 99%

Lack of association between body mass index and plasma adiponectin levels in healthy adults

Kuo

2011

Int J Obes

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Objectives: To test the hypothesis that obesity (increase in fat mass) independently affects the level of adipokines: adiponectin, tumor necrosis factor-a (TNFa) and interleukin (IL)-6. Methods: Publications in the past decade reporting adult plasma adiponectin, leptin, TNFa and/or IL-6 levels were compiled. Mean gender-specific values were extracted from studies that included medical screening to confirm physical health (43 groups, total 4852 subjects). Correlation analysis was conducted between adipokine levels and body mass index (BMI), a widely used estimate of adiposity. Results: For healthy lean to obese adults of both genders, no significant correlation between plasma adiponectin and BMI was detected. There was also no gender difference in plasma adiponectin level. In contrast, leptin levels showed a positive correlation with BMI in both genders, and women had significantly higher levels of plasma leptin consistent with a higher percentage of body fat. The proinflammatory cytokine TNFa failed to show correlation with BMI. Although IL-6 showed a positive correlation with BMI in women, the obesity-related increase was very limited. Conclusions: Data analysis based on studies performed on healthy adults did not support the hypothesis that obesity independently affects the plasma level of adiponectin and TNFa. Reported obesity-related changes in plasma adipokine levels may be a consequence of obesity-related metabolic disorders. Future studies are especially needed to understand the homeostasis of adiponectin.

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“…it was reported that the levels of IL-6 are elevated in liver injury patients, as well as in mice and rats with induced liver damage [15][16][17]25]. iL-6 levels are thus considered to be affected by factors other than liver damage.…”

Section: Discussionmentioning

confidence: 99%

Impairment of α<sub>2</sub>-Macroglobulin Synthesis in Experimental Hepatopathic Rats Treated with Turpentine Oil

et al. 2012

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Abstract:The aim of this study was to investigate the synthesis of α 2 -macroglobulin (α2M) in hepatopathic rats injected with turpentine oil to induce acute inflammation. Hepatopathy was induced by oral administration of acetaminophen at a dose of 1 g/kg daily for 2 weeks or a 25% solution of carbon tetrachloride (CCl 4 ) at 2 ml/kg body weight three times per week for 7 weeks. Acute inflammation was induced by intramuscular injection of turpentine oil at a dose of 1.0 ml/kg body weight. Serum concentrations of α2M were measured by enzyme-linked immunosorbent assay. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total protein differed significantly between acetaminophen or CCl 4 -induced hepatopathic rats and acetaminophen control (AA-control) or CCl 4 control (CC-control) rats. Furthermore, pathological examination confirmed hepatopathy in rat livers. Peak serum concentrations and area under the time-concentration curve for α2M showed significant differences between hepatopathic rats and AA-control or CC-control rats. Thus, serum concentrations of α2M did not increase when compared with nontreated rats.

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Cytokines as potential biomarkers of liver toxicity

Cited by 81 publications

References 101 publications

In-depth Identification of Pathways Related to Cisplatin-induced Hepatotoxicity through an Integrative Method Based on an Informatics-assisted Label-free Protein Quantitation and Microarray Gene Expression Approach

In-depth Identification of Pathways Related to Cisplatin-induced Hepatotoxicity through an Integrative Method Based on an Informatics-assisted Label-free Protein Quantitation and Microarray Gene Expression Approach

Lack of association between body mass index and plasma adiponectin levels in healthy adults

Impairment of α<sub>2</sub>-Macroglobulin Synthesis in Experimental Hepatopathic Rats Treated with Turpentine Oil

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